Outcomes of Premature Ventricular Contraction-Cardiomyopathy in the Veteran Population: A Secondary Analysis of the CHF-STAT Study.

OBJECTIVES: This study sought to assess the rate and outcomes of premature ventricular contractions (PVC)-cardiomyopathy from the CHF-STAT (Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure) trial, a population with cardiomyopathy (left ventricular [LV] ejection fraction of <40%) and frequent PVCs (>10 PVCs per hour). BACKGROUND: PVCs are associated with heart failure and PVC-cardiomyopathy. The prevalence of PVC-cardiomyopathy and outcome benefits of PVC suppression are not clear. METHODS: A secondary analysis of the CHF-STAT study was performed to compare the rate of successful PVC suppression (≥80% PVC reduction), LV recovery (defined as improvement in LV ejection fraction of ≥10% points), and PVC-cardiomyopathy between amiodarone and placebo groups at 6 months. PVC-cardiomyopathy was defined if both PVC reduction of ≥80% and LV ejection fraction improvement of ≥10% were present at 6 months. Cardiac events (death or resuscitated cardiac arrest) were compared between PVC-cardiomyopathy versus non-PVC-cardiomyopathy during a 5-year follow-up. RESULTS: The rates of successful PVC suppression and LV recovery were significantly higher in the amiodarone (72% and 39%, respectively) when compared to the placebo group (12% and 16%, respectively; p < 0.001), regardless of cardiomyopathy etiology. PVC-cardiomyopathy was present in 29% and 1.8% of patients in the amiodarone and placebo groups, respectively (p < 0.001). Similar PVC-cardiomyopathy rates were found in ischemic (24% amiodarone vs. 2% placebo; p < 0.001) and nonischemic populations (41% amiodarone vs. 1.5% placebo; p < 0.001). Death and resuscitated cardiac arrest were significantly lower in patients with PVC-cardiomyopathy and those treated with amiodarone. CONCLUSIONS: The overall prevalence of PVC-cardiomyopathy in the CHF-STAT study was significant regardless of ischemic substrate (29%, overall population; 41%, nonischemic cardiomyopathy). Treatment of PVC-cardiomyopathy with amiodarone is likely to improve survival in this high-risk population.

Digoxin Initiation and Outcomes in Patients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Digoxin reduces the risk of heart failure hospitalization in patients with heart failure with reduced ejection fraction. Less is known about this association in patients with heart failure with preserved ejection fraction (HFpEF), the examination of which was the objective of the current study. METHODS: In the Medicare-linked OPTIMIZE-HF registry, 7374 patients hospitalized for HF had ejection fraction ≥50% and were not receiving digoxin prior to admission. Of these, 5675 had a heart rate ≥50 beats per minute, an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 or did not receive inpatient dialysis, and digoxin was initiated in 524 of these patients. Using propensity scores for digoxin initiation, calculated for each of the 5675 patients, we assembled a matched cohort of 513 pairs of patients initiated and not initiated on digoxin, balanced on 58 baseline characteristics (mean age, 80 years; 66% women; 8% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin initiation were estimated in the matched cohort. RESULTS: Among the 1026 matched patients with HFpEF, 30-day heart failure readmission occurred in 6% and 9% of patients initiated and not initiated on digoxin, respectively (HR 0.70; 95% CI, 0.45-1.10; P = .124). HRs (95% CIs) for 30-day all-cause readmission and all-cause mortality associated with digoxin initiation were 0.95 (0.73-1.23; P = .689) and 0.93 (0.55-1.56; P = .773), respectively. Digoxin initiation had no association with 6-year outcomes. CONCLUSION: Digoxin initiation prior to hospital discharge was not associated with 30-day or 6-year outcomes in older hospitalized patients with HFpEF.

Prior Heart Failure Hospitalization and Outcomes in Patients with Heart Failure with Preserved and Reduced Ejection Fraction.

BACKGROUND: A prior hospitalization resulting from heart failure is associated with poor outcomes in ambulatory patients with heart failure. Less is known about this association in hospitalized patients with heart failure and whether it varies by ejection fraction. METHODS: Of the 25,345 hospitalized patients in the Medicare-linked OPTIMIZE-HF registry, 22,491 had known heart failure, of whom 7648 and 9558 had heart failure with preserved (≥50%) and reduced (≤40%) ejection fraction (HFpEF and HFrEF), respectively. Overall, 927 and 1862 patients with HFpEF and HFrEF had hospitalizations for heart failure during the 6 months before the index hospitalization, respectively. Using propensity scores for prior heart failure hospitalization, we assembled two matched cohorts of 924 pairs and 1844 pairs of patients with HFpEF and HFrEF, respectively, each balanced for 58 baseline characteristics. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes during 6 years of follow-up. RESULTS: Among 1848 matched patients with HFpEF, HRs (95% CIs) for all-cause mortality, all-cause readmission, and heart failure readmission were 1.35 (1.21-1.50; P <0.001), 1.34 (1.21-1.47; P <0.001), and 1.90 (1.67-2.16; P <0.001), respectively. Respective HRs (95% CIs) in 3688 matched patients with HFrEF were 1.17 (1.09-1.26; P <0.001), 1.32 (1.23-1.41; P <0.001), and 1.48 (1.37-1.61; P <0.001). CONCLUSIONS: Among hospitalized patients with heart failure, a previous hospitalization for heart failure is associated with higher risks of mortality and readmission in both HFpEF and HFrEF. The relative risks of death and heart failure readmission appear to be higher in HFpEF than in HFrEF.

Early Effects of Starting Doses of Enalapril in Patients with Chronic Heart Failure in the SOLVD Treatment Trial.

BACKGROUND: In the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical benefits were observed between starting doses of enalapril and the target dose achieved by postrandomization up-titration. In our current analysis, protecting the randomization, we examined the early effects of starting doses of enalapril. METHODS: There were 2569 patients with mild-to-moderate chronic heart failure with reduced ejection fraction (ejection fraction ≤35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril (n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose (20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration, which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the enalapril group were estimated. RESULTS: HRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined endpoint of heart failure hospitalization or all-cause mortality at 14 days after randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively. Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and 0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses of enalapril is similar to its previously reported long-term effects at the target dose. CONCLUSION: These data suggest that in stable ambulatory patients with heart failure with reduced ejection fraction, the magnitude of the early effect of starting doses of enalapril is similar to that observed during longer-term therapy with the target doses of the drug.

Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: National guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg. OBJECTIVES: This study sought to determine associations of SBP <130 mm Hg with outcomes in patients with HFrEF. METHODS: Of the 25,345 patients in the Medicare-linked OPTIMIZE-HF registry, 10,535 had an ejection fraction (EF) ≤40%. Of these, 5,615 had stable SBP (≤20 mm Hg admission to discharge variation), and 3,805 (68%) had a discharge SBP <130 mm Hg. Propensity scores for SBP <130 mm Hg, estimated for each of the 5,615 patients, were used to assemble a matched cohort of 1,189 pairs of patients with SBP <130 versus ≥130 mm Hg, balanced on 58 baseline characteristics (mean age 76 years; mean EF 28%, 45% women, 13% African American). This process was repeated in 3,946 patients, after excluding 1,669 patients (30% of 5,615) with a discharge SBP <110 mm Hg and assembled a second matched balanced cohort of 1,099 pairs of patients with SBP 110 to 129 mm Hg versus ≥130 mm Hg. RESULTS: Thirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio [HR]: 1.76; 95% confidence interval [CI]: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively. CONCLUSIONS: Among hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF.

Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: Lower systolic blood pressure (SBP) levels are associated with poor outcomes in patients with heart failure. Less is known about this association in heart failure with preserved ejection fraction (HFpEF). Objective: To determine the associations of SBP levels with mortality and other outcomes in HFpEF. Design, Setting, and Participants: A propensity score-matched observational study of the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry included 25 354 patients who were discharged alive; 8873 (35.0%) had an ejection fraction of at least 50%, and of these, 3915 (44.1%) had stable SBP levels (≤20 mm Hg admission to discharge variation). Data were collected from 259 hospitals in 48 states between March 1, 2003, and December 31, 2004. Data were analyzed from March 1, 2003, to December 31, 2008. Exposure: Discharge SBP levels less than 120 mm Hg. A total of 1076 of 3915 (27.5%) had SBP levels less than 120 mm Hg, of whom 901 (83.7%) were matched by propensity scores with 901 patients with SBP levels of 120 mm Hg or greater who were balanced on 58 baseline characteristics. Main Outcomes and Measures: Thirty-day, 1-year, and overall all-cause mortality and heart failure readmission through December 31, 2008. Results: The 1802 matched patients had a mean (SD) age of 79 (10) years; 1147 (63.7%) were women, and 134 (7.4%) were African American. Thirty-day all-cause mortality occurred in 91 (10%) and 45 (5%) of matched patients with discharge SBP of less than 120 mm Hg vs 120 mm Hg or greater, respectively (hazard ratio [HR], 2.07; 95% CI, 1.45-2.95; P < .001). Systolic blood pressure level less than 120 mm Hg was also associated with a higher risk of mortality at 1 year (39% vs 31%; HR, 1.36; 95% CI, 1.16-1.59; P < .001) and during a median follow-up of 2.1 (overall 6) years (HR, 1.17; 95% CI, 1.05-1.30; P = .005). Systolic blood pressure level less than 120 mm Hg was associated with a higher risk of heart failure readmission at 30 days (HR, 1.47; 95% CI, 1.08-2.01; P = .02) but not at 1 or 6 years. Hazard ratios for the combined end point of heart failure readmission or all-cause mortality associated with SBP level less than 120 mm at 30 days, 1 year, and overall were 1.71 (95% CI, 1.34-2.18; P < .001), 1.21 (95% CI, 1.07-1.38; P = .004), and 1.12 (95% CI, 1.01-1.24; P = .03), respectively. Conclusions and Relevance: Among hospitalized patients with HFpEF, an SBP level less than 120 mm Hg is significantly associated with poor outcomes. Future studies need to prospectively evaluate optimal SBP treatment goals in patients with HFpEF.

Heart Rate and Outcomes in Hospitalized Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: A lower heart rate is associated with better outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Less is known about this association in patients with HF with preserved ejection fraction (HFpEF). OBJECTIVES: The aims of this study were to examine associations of discharge heart rate with outcomes in hospitalized patients with HFpEF. METHODS: Of the 8,873 hospitalized patients with HFpEF (EF ≥50%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 6,286 had a stable heart rate, defined as ≤20 beats/min variation between admission and discharge. Of these, 2,369 (38%) had a discharge heart rate of <70 beats/min. Propensity scores for discharge heart rate <70 beats/min, estimated for each of the 6,286 patients, were used to assemble a cohort of 2,031 pairs of patients with heart rate <70 versus ≥70 beats/min, balanced on 58 baseline characteristics. RESULTS: The 4,062 matched patients had a mean age of 79 ± 10 years, 66% were women, and 10% were African American. During 6 years (median 2.8 years) of follow-up, all-cause mortality was 65% versus 70% for matched patients with a discharge heart rate <70 versus ≥70 beats/min, respectively (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93; p < 0.001). A heart rate <70 beats/min was also associated with a lower risk for the combined endpoint of HF readmission or all-cause mortality (HR: 0.90; 95% CI: 0.84 to 0.96; p = 0.002), but not with HF readmission (HR: 0.93; 95% CI: 0.85 to 1.01) or all-cause readmission (HR: 1.01; 95% CI: 0.95 to 1.08). Similar associations were observed regardless of heart rhythm or receipt of beta-blockers. CONCLUSIONS: Among hospitalized patients with HFpEF, a lower discharge heart rate was independently associated with a lower risk of all-cause mortality, but not readmission.

Outcomes of cardiac resynchronization therapy in patients with intermittent atrial fibrillation or atrial flutter in the COMPANION trial.

BACKGROUND: Controlled clinical trial data are lacking for cardiac resynchronization therapy (CRT) outcomes in patients with advanced heart failure (HF) from reduced left ventricular ejection fraction (HFrEF) and intermittent atrial fibrillation or flutter (IAF/AFL). OBJECTIVE: The purpose of this study was to describe CRT outcomes in patients with IAF/AFL and advanced HF. METHODS: HF outcomes in patients in the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial with New York Heart Association class III or IV HFrEF, left ventricular ejection fraction ≤0.35, sinus rhythm at randomization, and no history of baseline arrhythmia were compared with those with a history of IAF/AFL. RESULTS: In those with no history of baseline arrhythmia (n = 887), compared with optimal pharmacological therapy (OPT) with no CRT, the CRT + OPT arms exhibited a significant reduction in the end points of death or any hospitalization (hazard ratio [HR] 0.73 [95% Confidence Interval (CI): 0.60 to 0.89]; P = .002) and death or HF hospitalization (HR 0.53 [95% CI: 0.41 to 0.68]; P < .001). In contrast, in the IAF/AFL subgroup (n = 293), CRT did not result in improved outcomes compared with OPT (death or any hospitalization: HR 1.16 [95% CI: 0.83 to 1.63]; P = .38; death or HF hospitalization: HR 0.97 [95% CI: 0.64 to 1.46]; P = .88). The interaction between history of AF/AFL and CRT was statistically significant for both outcomes (P < .05). CONCLUSION: In the COMPANION trial, patients with moderate to severe HFrEF and a history of IAF/AFL had no benefit from CRT.

Drug-induced post-repolarization refractoriness as an antiarrhythmic principle and its underlying mechanism.

AIMS: We hypothesized that amiodarone (AM), unlike d-sotalol (DS) (a 'pure' Class III agent), not only prolongs the action potential duration (APD) but also causes post-repolarization refractoriness (PRR), thereby preventing premature excitation and providing superior antiarrhythmic efficacy. METHODS AND RESULTS: We tested this hypothesis in 31 patients with inducible ventricular tachycardia (VT) during programmed stimulation with the use of the 'Franz' monophasic action potential (MAP) catheter with simultaneous pacing capability. We determined the effective refractory period (ERP) for each of three extrastimuli (S2-S4) and the corresponding MAP duration at 90% repolarization (APD90), both during baseline and on randomized therapy with either DS (n = 15) or AM (n = 16). We defined ERP > APD90 as PRR and ERP < APD90 as 'encroachment' on repolarization. A revised computer action potential model was developed to help explain the mechanisms of these in-vivo human-heart phenomena. Encroachment but not PRR was present in all patients at baseline and during DS treatment (NS vs. baseline), and VT was non-inducible in only 2 of 15 DS patients. In contrast, in 12 of 16 AM patients PRR was present (P < 0.001 vs. baseline), and VT was no longer inducible. Our model (with revised sodium channel kinetics) reproduced encroachment and drug-induced PRR. CONCLUSION: Both, AM and DS, prolonged APD90 but only AM produced PRR and prevented encroachment of premature extrastimuli. Our computer simulations suggest that PRR is due to altered kinetics of the slow inactivation of the rapid sodium current. This may contribute to the high antiarrhythmic efficacy of AM.

Costs and clinical consequences of suboptimal atrial fibrillation management.

Atrial fibrillation (AF) places a considerable burden on the US health care system, society, and individual patients due to its associated morbidity, mortality, and reduced health-related quality of life. AF increases the risk of stroke, which often results in lengthy hospital stays, increased disability, and long-term care, all of which impact medical costs. An expected increase in the prevalence of AF and incidence of AF-related stroke underscores the need for optimal management of this disorder. Although AF treatment strategies have been proven effective in clinical trials, data show that patients still receive suboptimal treatment. Adherence to AF treatment guidelines will help to optimize treatment and reduce costs due to AF-associated events; new treatments for AF show promise for future reductions in disease and cost burden due to improved tolerability profiles. Additional research is necessary to compare treatment costs and outcomes of new versus existing agents; an immediate effort to optimize treatment based on existing evidence and guidelines is critical to reducing the burden of AF.

Spontaneous coronary artery dissection: aggressive vs. conservative therapy.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a rare condition that commonly presents as an acute coronary event in the younger population, especially in females of childbearing age. Generally, there is no consensus on the etiology, prognosis, and treatment of SCAD. METHODS: The Medline database was searched for "spontaneous coronary artery dissection" between 1931 and 2008. A total of 440 cases of SCAD were identified. Demographic data were analyzed with either the Student's t-test or the chi-square test for categorical and nominal variables, respectively. Kaplan-Meier outcome analysis was used to assess the outcome of a given treatment for all patients after 1990. RESULTS: SCAD was found more commonly in females with 308 (70%) cases. Pregnancy was associated with SCAD in 80 (26.1%) cases. Among pregnant patients, 67 (83.8%) developed SCAD in the postpartum period and 13 (16.2%) patients in the prepartum period. Analysis of treatment modalities showed that 21.2% of the patients who were conservatively managed after the initial diagnosis eventually required surgical or catheter-based intervention compared to 2.5% of patients who were initially treated with an aggressive strategy. Kaplan-Meier analysis showed that patients with an isolated single lesion in left or right coronary artery had a statistically significant better outcome when treated with an early aggressive strategy, including coronary artery bypass grafting (CABG) or stent placement as compared to a conservative strategy (p = 0.023, p = 0.006, respectively). CONCLUSION: Early intervention with either CABG or percutaneous coronary intervention following the diagnosis of SCAD leads to a better outcome and less need for further intervention.

Long-term mortality outcomes according to the frequency of right ventricular pacing in veterans.

Background. Right ventricular pacing (RVP) has been associated with adverse outcomes, including heart failure and death. Minimizing RVP has been proposed as a therapeutic goal for a variety of pacing devices and indications. Objective. Quantify survival according to frequency of RVP in veterans with pacemakers. Methods. We analyzed electrograms from transtelephonic monitoring of veterans implanted with pacemakers between 1995 and 2005 followed by the Eastern Pacemaker Surveillance Center. We compared all cause mortality and time to death between patients with less than 20% and more than 80% RVP. Results. Analysis was limited to the 7198 patients with at least six trans-telephonic monitoring records (mean = 21). Average follow-up was 5.3 years. Average age at pacemaker implant was significantly lower among veterans with <20% RVP (67 years versus 72 years; P < .0001). An equal proportion of deaths during follow-up were noted for each group: 126/565 patients (22%) with <20% RVP and 1113/4968 patients (22%) with >80% RVP. However, average post-implant survival was 4.3 years with <20% RVP versus 4.7 years with >80% RVP (P < .0001). Conclusions. Greater frequency (>80%) of RVP was not associated with higher mortality in this population of veterans. Those veterans utilizing <20% RVP had a shortened adjusted survival rate (P = .0016).

Intrathoracic impedance preceding ventricular tachyarrhythmia episodes.

BACKGROUND: Heart failure is associated with ventricular tachyarrhythmias (VT/VF). Fluid accumulation during worsened heart failure may trigger VT/VF. Increased intrathoracic impedance has been correlated with fluid accumulation during heart failure. Implanted defibrillators capable of daily measures of intrathoracic impedance allow correlation of impedance with occurrence of VT/VF. We hypothesized that VT/VF episodes are preceded by decreases in intrathoracic impedance. The goal was to identify the relationship of intrathoracic impedance measured by implanted cardioverter defibrillators to the occurrence of VT/VF. METHOD: Implanted defibrillator follow-up data were obtained retrospectively. Those with Medtronic OptiVol (Medtronic Inc., Minneapolis, MN, USA), storing averaged daily and reference impedance values, were reviewed for VT/VF episodes. Impedance changes in the week leading up to VT/VF were analyzed. RESULTS: A total of 317 VT/VF episodes in a cohort of 121 patients' follow-up data were evaluated. Averaged daily intrathoracic impedance declined preceding 64% of VT/VF episodes, with an average decline of 0.46 +/- 0.35 Ohms from the day before the VT/VF episodes. However, the mean values of the averaged daily and reference impedance did not change significantly. A novel measure, DeltaTI, the sum of the daily differences between the averaged daily and reference impedance, was negative preceding 66% of VT/VF episodes (P < 0.001). The mean DeltaTI was -4.0 +/- 1.3 Ohms, which was significantly lower than the theoretically expected value of zero Ohms (P < 0.01). CONCLUSION: (1) Averaged daily impedance declined preceding 64% of VT/VF episodes, but the overall decline was of small magnitude; (2) a novel measure, DeltaTI, was negative preceding 66% of VT/VF episodes, and significantly below zero.

The burden and management of TIA and stroke in the Veterans Administration and Department of Defense.

Transient ischemic attack (TIA) and stroke are commonly occurring cerebrovascular events that require prompt and appropriate treatment to reduce the risk of secondary stroke. The US Department of Veterans Affairs (VA) and the Department of Defense constitute 2 large medical systems treating military personnel, both active and retired, as well as many of their dependents. In the area of stroke and TIA management, the VA in particular has instituted far-reaching measures, including those to ensure adherence to clinical treatment guidelines shown to produce optimal outcomes in stroke. The result of these measures has been that VA patients experience lower morbidity and mortality risk, as well as lower rates of stroke-related rehospitalization, than comparable patients treated through Medicare and Medicaid and in university hospitals. These successes in part may be an advantage derived from a relatively closed system with sufficient administrative discipline to maintain clinical guidelines treatment standards. It may also be the case that continuity of care in these systems produces better outcomes than more fragmentary treatment that may be experienced in the civilian realm. In addition, the VA system avoids incentivizing physicians for performing medical services, and instead incentivizes quality of care, which may provide a further advantage for patients treated within that system.

Systematic electrocardioversion for atrial fibrillation and role of antiarrhythmic drugs: a substudy of the SAFE-T trial.

BACKGROUND: Energy levels for electrocardioversion in atrial fibrillation (AF) have been empiric, and the influence of antiarrhythmic therapy compared with placebo is largely unknown. OBJECTIVE: The purpose of this study was to determine systematically the energy levels for electrocardioversion in patients with persistent AF and to define the influence of antiarrhythmic therapy. METHODS: Patients (n = 665) with persistent AF were randomized to amiodarone, sotalol, or placebo. Rate control, if necessary, was achieved with digoxin, diltiazem, or verapamil. Among the 665 patients, 504 who did not achieve sinus rhythm at day 28 had electrocardioversion systematically by a prespecified four-step protocol as follows: monophasic shocks-100, 200, 360, 360 J; or biphasic shocks-150, 175, 200, 200 J sequentially. Energy levels and shock waveforms (monophasic/biphasic) for successful electrocardioversion (sinus rhythm for at least 1 minute) and use of antiarrhythmic therapy and calcium channel blockers were recorded. RESULTS: Electrocardioversion was successful in 371 (71.6%) of 504 patients: 72%, 73.5%, and 67.9% for patients assigned to amiodarone, sotalol, and placebo, respectively. Overall, after adjustments for age, body mass index (BMI), history of AF, shock waveforms, left atrial size, and ejection fraction, both amiodarone (odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.24-3.77, P <.01) and sotalol (OR: 1.92, 95% CI: 1.11-3.33, P = .02) significantly facilitated successful electrocardioversion compared with placebo. Calcium channel blockers had no effect on the success rate of electrocardioversion. Success of electrocardioversion was associated with lower BMI, AF history < or =1 year, and older age. Compared with placebo, patients taking amiodarone were significantly more likely to achieve successful electrocardioversion in step 1 (OR: 2.73, 95% CI: 1.11-6.74, P = .03) and step 3 (OR: 1.86, 95% CI: 1.00-3.44, P = .05) but not in steps 2 and 4. Sotalol was superior to placebo in step 4 (OR: 2.58, 95% CI: 1.02-6.52, P = .05) and trended in step 2 (OR: 1.7, 95% CI: 0.98-3.07, P = .06). Successful electrocardioversion was seen in 11%, 29%, 38%, and 29% in steps 1, 2, 3, and 4, respectively. Compared with monophasic shocks, biphasic shocks achieved higher success rates for step 1 (P <.001) and step 2 (P <.01), respectively. Antiarrhythmic therapy did not influence the total number of energy steps used for the patients with successful electrocardioversion. However, biphasic shocks, lower BMI, and AF duration < or =1 year were associated with less energy step used for successful cardioversion. CONCLUSION: Amiodarone and sotalol facilitated successful electrocardioversion, which could be achieved in a stepwise fashion. Upon achievement of successful electrocardioversion, amiodarone is superior to placebo, and sotalol has a lesser effect. Antiarrhythmic drugs had no effect on the total number of energy step use in patients who had successful electrocardioversion. Calcium channel blockers had no influence on the success rate in achieving sinus rhythm. Successful electrocardioversion was associated with lower BMI and AF history < or =1 year. Lower energy use was associated with biphasic shocks, lower BMI, and AF duration < or =1 year.

Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation.

BACKGROUND: Many patients receiving amiodarone therapy are male. The long-term risk for amiodarone-induced thyroid dysfunction in these patients has not been systematically and prospectively investigated. The purpose of this study was to determine the extent of amiodarone-induced thyroid dysfunction in a large male cohort. METHODS: This is a substudy of a prospective randomized controlled trial (SAFE-Trial) in which amiodarone, sotalol, and placebo for persistent atrial fibrillation were evaluated. For the purpose of this substudy, sotalol and placebo groups were combined into a control group. Serial thyroid function tests were performed over 1-4.5 years. Of the 665 patients enrolled in the SAFE-Trial, 612 patients were included in this sub-study. RESULTS: Subclinical hypothyroidism, thyroid-stimulating hormone (TSH) level 4.5-10 mU/L, was seen among 25.8% of the amiodarone-treated patients and only 6.6% of controls (P <.0001). Overt hypothyroidism, TSH level >10 mU/L, was seen among 5.0% of the amiodarone-treated patients, and only 0.3% of controls (P <.001). By 6 months, 93.8% of the patients who developed TSH elevations above 10 mU/L on amiodarone had been detected. There was a trend toward a greater proportion of hyperthyroidism, defined as a TSH <0.35 mU/L, in the amiodarone group compared with the control group (5.3% vs 2.4%, P=.07). CONCLUSIONS: Hypothyroidism developed in 30.8% of older males treated with amiodarone and in only 6.9% of the controls. Hypothyroidism presented at an early stage of therapy. Hyperthyroidism occurred in 5.3% of amiodarone treated patients, and was a subclinical entity in all but 1 case.

Exercise capacity in atrial fibrillation: a substudy of the Sotalol-Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T).

BACKGROUND: Therapy for chronic atrial fibrillation (AF) focuses on rate versus rhythm control, but little is known about the effects of common therapeutic interventions on exercise tolerance in AF. METHODS: Six hundred fifty-five patients with chronic AF underwent maximal exercise testing at baseline and 8 weeks, 6 months, and 1 year after randomization to sotalol, amiodarone, or placebo therapy and attempted direct current cardioversion. Analyses of baseline determinants of exercise capacity, predictors of change in exercise capacity at 6 months and 1 year, and the short- and long-term effects of cardioversion on exercise capacity were made. RESULTS: Age, obesity, and presence of symptoms accompanying AF were inversely associated with baseline exercise capacity, but these factors accounted for only 10% of the variance in exercise capacity. Patients most likely to benefit from cardioversion were those most limited initially, younger, not obese or hypertensive, and with an uncontrolled ventricular rate at baseline. Conversion to sinus rhythm (SR) resulted in significant reductions in resting (approximately 25 beat/min) and peak exercise (approximately 40 beat/min) heart rates at 6 months and 1 year (P < .001). Successful cardioversion improved exercise capacity by 15% at 8 weeks, and these improvements were maintained throughout the year. This improvement was observed both among those who maintained SR and those with intermittent AF. CONCLUSION: Cardioversion resulted in a sustained improvement in exercise capacity over the course of 1 year, and this improvement was similar between those in SR and those with SR and recurrent AF. Patients most likely to improve with treatment tended to be younger and nonobese and have the greatest limitations initially.

Role of amiodarone or implantable cardioverter/defibrillator in patients with atrial fibrillation and heart failure.

BACKGROUND: Heart failure complicated by atrial fibrillation (AF) is associated with excessive mortality and morbidity. The aim of the study was to determine the role of amiodarone or implantable cardioverter/defibrillator (ICD) in patients with AF and heart failure. METHODS: Patients were determined to be in sinus rhythm (SR) or AF on the baseline electrocardiogram. Mortality, ICD discharge, or change in rhythm was assessed. RESULTS: Of the 2521 patients at baseline, 2328 were in SR and 173 were in AF. Overall, after adjusting for differences in baseline variables, there was no difference in mortality between patients with SR and patients with AF (P = .98), nor within assigned groups: placebo (P) (P = .82), amiodarone (A) (P = .68), and ICD (P = .40). For patients with SR, ICD decreased mortality (P vs ICD, P = .004; A vs ICD, P = .004; P vs A, P = .75). For patients with AF, there were no differences in mortality among groups (P vs ICD, P = .99; A vs ICD, P = .88; P vs A, P = .88). Of patients with SR at baseline, 11% (264) developed AF by any electrocardiogram during follow-up (P 12%, A 8%, ICD 15%; A vs P, P = .019; A vs ICD, P = .001; P vs ICD, P = .044). Of patients with AF, 70% (121) developed SR during follow-up (P 66%, A 67%, ICD 75%, all P = not significant against each other). Any ICD shock was seen in 52% (34) of patients with AF vs 30% (222) of patients with SR (P = .001). Inappropriate shocks were seen in 37% (24) of patients with AF vs 14% (107) of patients with SR (P = .001). Appropriate shocks were more often seen in AF vs SR (P = .03). CONCLUSION: After adjustments for baseline differences, patients with AF and patients with SR have similar overall mortality rates. Compared to P or A, ICD improves survival in patients with SR, but may not in patients with AF. Amiodarone is effective in reducing new AF, but not in converting AF to SR. Implantable cardioverter/defibrillator, inappropriate, and appropriate shocks were more often seen in AF than in SR.

Quality of life and exercise performance in patients in sinus rhythm versus persistent atrial fibrillation: a Veterans Affairs Cooperative Studies Program Substudy.

OBJECTIVES: The purpose of this study was to determine quality of life (QOL) and exercise performance (EP) in patients with persistent atrial fibrillation (AF) converted to sinus rhythm (SR) compared with those remaining in or reverting to AF. BACKGROUND: Restoration of SR in patients with AF improving QOL and EP remains controversial. METHODS: Patients with persistent AF were randomized double-blind to amiodarone, sotalol, or placebo. Those not achieving SR at day 28 were cardioverted and classified into SR or AF groups at 8 weeks (n = 624) and 1 year (n = 556). The QOL (SF-36), symptom checklist (SCL), specific activity scale (SAS), AF severity scale (AFSS), and EP were assessed. RESULTS: Favorable changes were seen in SR patients at 8 weeks in physical functioning (p < 0.001), physical role limitations (p = 0.03), general health (p = 0.002), and vitality (p < 0.001), and at 1 year in general health (p = 0.007) and social functioning (p = 0.02). Changes in the scores for SCL severity (p = 0.01), functional capacity (p = 0.003), and AFSS symptom burden (p < 0.001) at 8 weeks and in SCL severity (p < 0.01) and AF symptom burden (p < 0.001) at 1 year showed significant improvements in SR versus AF. Symptomatic patients were more likely to have improvement. The EP in SR versus AF was greater from baseline to 8 weeks (p = 0.01) and to 1 year (p = 0.02). The EP correlated with physical functioning and functional capacity except in the AF group at 1 year. CONCLUSIONS: In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.